The effect of opting-in versus opting-out forming on the rate of reported variants of questionable significance in prenatal microarray.

Objective: To examine the effect of patient-selected opt-in versus opt-out option on the rate of reported variants of uncertain clinical significance (VOUS) and high-frequency low-penetrant (HFLP) findings in prenatal microarray testing.

Methods: A standard microarray consent form in Israel includes a requirement to note patient choice to be or not to be informed about the presence of VOUS and HFLP variants. The original form was designed as an opting-out method, in which the women had to actively mark if they did not want to be informed about questionable findings.

Seeing is believing: Correlating optoelectronic functionality with atomic scale imaging of single semiconductor nanocrystals.

A unique on-chip method for the direct correlation of optical properties, with atomic-scale chemical-structural characteristics for a single quantum dot (QD), is developed and utilized in various examples. This is based on performing single QD optical characterization on a modified glass substrate, followed by the extraction of the relevant region of interest by focused-ion-beam-scanning electron microscope processing into a lamella for high resolution scanning transmission electron microscopy (STEM) characterization with atomic scale resolution. The direct correlation of the optical response under an electric field with STEM analysis of the same particle allows addressing several single particle phenomena: first, the direct correlation of single QD photoluminescence (PL) polarization and its response to the external field with the QD crystal lattice alignment, so far inferred indirectly; second, the identification of unique yet rare few-QD assemblies, correlated directly with their special spectroscopic optical characteristics, serving as a guide for future designed assemblies; and third, the study on the effect of metal island growth on the PL behavior of hybrid semiconductor-metal nanoparticles, with relevance for their possible functionality in photocatalysis.

[HOW SIMPLE IS "SIMPLE" GENETIC COUNSELING?].

Introduction: Genetic counselors are often compared with other medical professionals in terms of productivity, based on the number of patients seen and the time required for each patient. Prenatal genetic counseling before amniocentesis in uneventful pregnancies is considered to be a "simple" counseling, with potentially less time required for each patient. Thus, in some medical centers the duration of such consultations is limited to provide only the basic explanation without detailed collection of personal and family history, while in others the explanation is given to several patients together.

The anxiety caused by abnormal results of Down syndrome screening tests.

The objective of our survey was to evaluate the anxiety experienced by women receiving abnormal results of prenatal Down syndrome screening by an electronic anonymous survey. Anxiety level was evaluated by a six-item Spielberger State-Trait Anxiety Inventory. Of 559 respondents, high anxiety scores were reported in the majority (86.

Biallelic ADAM22 pathogenic variants cause progressive encephalopathy and infantile-onset refractory epilepsy.

Pathogenic variants in A Disintegrin And Metalloproteinase (ADAM) 22, the postsynaptic cell membrane receptor for the glycoprotein leucine-rich repeat glioma-inactivated protein 1 (LGI1), have been recently associated with recessive developmental and epileptic encephalopathy. However, so far, only two affected individuals have been described and many features of this disorder are unknown. We refine the phenotype and report 19 additional individuals harbouring compound heterozygous or homozygous inactivating ADAM22 variants, of whom 18 had clinical data available.

Diagnostic yield and recognized barriers of an adult neurogenetics clinic.

The advent of molecular genetic technologies paved a path for the diagnosis of many neurological disorders. Joint evaluation by a neurologist and a medical genetics specialist can potentially increase diagnostic effectiveness by ensuring the exclusion of non-genetic conditions with similar phenotypes and by rationally selecting appropriate genetic diagnostic tools. Therefore, a monthly adult neurogenetics clinic was established.

A novel truncating variant in the FGD1 gene associated with Aarskog-Scott syndrome in a family previously diagnosed with Tel Hashomer camptodactyly.

Tel Hashomer camptodactyly syndrome is a long-known entity characterized by camptodactyly with muscular hypoplasia, skeletal dysplasia, and abnormal palmar creases. Currently, the genetic basis for this disorder is unknown, thus there is a possibility that this clinical presentation may be contained within another genetic diagnosis. Here, we present a multiplex family with a previous clinical diagnosis of Tel Hashomer camptodactyly syndrome.

The effect of polyhydramnios degree on chromosomal microarray results: a retrospective cohort analysis of 742 singleton pregnancies.

Purpose: To analyze the risk for clinically significant microarray aberrations in pregnancies with polyhydramnios.

Methods: Data from all chromosomal microarray analyses (CMA) performed due to polyhydramnios between January 2013 and December 2019 were retrospectively obtained from the Ministry of Health Database. The rate of clinically significant (pathogenic and likely pathogenic) CMA findings in isolated and non-isolated polyhydramnios cohorts was compared to a local control group of 5541 fetuses with normal ultrasound, in which 78 (1.

Spectrum of genes for inherited hearing loss in the Israeli Jewish population, including the novel human deafness gene ATOH1.

Mutations in more than 150 genes are responsible for inherited hearing loss, with thousands of different, severe causal alleles that vary among populations. The Israeli Jewish population includes communities of diverse geographic origins, revealing a wide range of deafness-associated variants and enabling clinical characterization of the associated phenotypes. Our goal was to identify the genetic causes of inherited hearing loss in this population, and to determine relationships among genotype, phenotype, and ethnicity.

A novel mutation in MYCN gene causing congenital absence of the flexor pollicis longus tendon as an unusual presentation of Feingold syndrome 1.

Feingold syndrome 1 (FGLDS1) is an autosomal dominant malformation syndrome, characterized by skeletal anomalies, microcephaly, facial dysmorphism, gastrointestinal atresias and learning disabilities. Mutations in the MYCN gene are known to be the cause of this syndrome. Congenital absence of the flexor pollicis longus (CAFPL) tendon is a rare hand anomaly.

Genetic counseling of high-risk isolated populations: A worldwide challenge.

Background: Isolated populations with high rates of consanguinity and genetic disorders can be found in most parts of the world. The aim of our paper was to highlight the unique challenges faced in genetic counseling for such patients and to discuss the ways to facilitate the difficulties, with an emphasis on the crucial role of electronic medical records (EMR).

Case: We report a couple presenting with elevated maternal alpha-fetoprotein in three pregnancies, in which an erroneous diagnosis of epidermolysis bullosa was established in the past and carried along through several years.

A novel heterozygous loss-of-function DCC Netrin 1 receptor variant in prenatal agenesis of corpus callosum and review of the literature.

Agenesis of the corpus callosum (ACC) is a common prenatally-detected brain anomaly. Recently, an association between mutations in the DCC Netrin 1 receptor (DCC) gene and ACC, with or without mirror movements, has been demonstrated. In this manuscript, we present a family with a novel heterozygous frameshift mutation in DCC, review the available literature, and discuss the challenges involved in the genetic counseling for recently discovered disorders with paucity of medical information.

The rare 13q33-q34 microdeletions: eight new patients and review of the literature.

The objective of this study is to shed light on the phenotype and inheritance pattern of rare 13q33-q34 microdeletions. Appropriate cases were retrieved using local databases of two largest Israeli centers performing CMA analysis. In addition, literature search in PubMed, DECIPHER and ClinVar databases was performed.

Whole-exome sequencing reveals a novel missense mutation in the MARS gene related to a rare Charcot-Marie-Tooth neuropathy type 2U.

Charcot-Marie-Tooth (CMT) is a heterogeneous group of progressive disorders, characterized by chronic motor and sensory polyneuropathy. This hereditary disorder is related to numerous genes and varying inheritance patterns. Thus, many patients do not reach a final genetic diagnosis.

Autosomal recessive Noonan syndrome associated with biallelic LZTR1 variants.

Purpose: To characterize the molecular genetics of autosomal recessive Noonan syndrome.

Methods: Families underwent phenotyping for features of Noonan syndrome in children and their parents. Two multiplex families underwent linkage analysis.

Microarray analysis in pregnancies with isolated unilateral kidney agenesis.

BackgroundThe objective of our study was to examine the risk for submicroscopic chromosomal aberrations among fetuses with apparently isolated solitary kidney.MethodsData acquisition was performed retrospectively by searching Israeli Ministry of Health-computerized database. All cases having chromosomal microarray analysis (CMA), referred because of an indication of isolated unilateral kidney agenesis between January 2013 and September 2016, were included.

First-Trimester Crown-Rump Length and Risk of Chromosomal Aberrations-A Systematic Review and Meta-analysis.

Importance: Lower than expected first-trimester crown-rump length (CRL) is a common sonographic finding, usually leading to reassessment of gestational age.

Objective: The aim of this study was to perform a meta-analysis defining the risk of chromosomal aberrations in pregnancies with decreased first-trimester CRL.

Evidence Acquisition: A search was conducted by a research librarian in 5 databases, with no time or language restrictions.

Risk for chromosomal aberrations in apparently isolated intrauterine growth restriction: A systematic review.

Objective: To perform a systematic review examining the risk of chromosomal aberrations in apparently isolated intrauterine growth restriction (IUGR).

Methods: Search was conducted by research librarian in 5 databases. By independent screening of 2894 references, 2 investigators selected original studies examining the risk of chromosomal aberrations in apparently isolated IUGR diagnosed at the second and third trimesters by using ultrasound.

The yield and complications of amniocentesis performed after 24 weeks of gestation.

Purpose: This study assessed the use and complications of late amniocentesis (AC) and analyzed factors that affect complication rate.

Methods: A retrospective analysis of 167 genetic AC performed after 24 weeks during a 10-year period in two medical centers was conducted. Data regarding the indications for AC, genetic work-up, and pregnancy outcomes were retrieved from patient medical records and telephone-based questionnaires.

Whole-Exome Sequencing Identifies a Novel Homozygous Frameshift Mutation in the MTMR2 Gene as a Causative Mutation in a Patient with Charcot-Marie-Tooth Disease Type 4B1.

Charcot-Marie-Tooth (CMT) disease refers to a heterogeneous group of axonal and demyelinating polyneuropathies, characterized by chronic motor and sensory dysfunction. CMT is the most common genetic cause of neuropathy. The present study aimed to identify the gene mutation responsible for CMT in Ashkenazi Jew (AJ) patient.

Spectrum of mutations in the renin-angiotensin system genes in autosomal recessive renal tubular dysgenesis.

Autosomal recessive renal tubular dysgenesis (RTD) is a severe disorder of renal tubular development characterized by early onset and persistent fetal anuria leading to oligohydramnios and the Potter sequence, associated with skull ossification defects. Early death occurs in most cases from anuria, pulmonary hypoplasia, and refractory arterial hypotension. The disease is linked to mutations in the genes encoding several components of the renin-angiotensin system (RAS): AGT (angiotensinogen), REN (renin), ACE (angiotensin-converting enzyme), and AGTR1 (angiotensin II receptor type 1).

Power spectral analysis of heart rate variability during the 100-g oral glucose tolerance test in pregnant women.

Objective: The aims of the present study were to 1) evaluate autonomic function during the oral glucose tolerance test (OGTT) in pregnant women and 2) investigate whether gestational diabetes mellitus (GDM) modifies autonomic control of heart rate variability.

Research Design And Methods: We prospectively studied 27 pregnant women (15 without GDM, 12 with GDM) during a 100-g OGTT. The maternal electrocardiogram was recorded before and 60 min after glucose ingestion, when peak glucose levels are expected.

[Is there an association between PUPPP and preeclampsia, abruptio placentae and fetal death?].

This is a case study of a 28-year old woman, gravida 1 para 0, presented at 37+4 weeks gestation due to purpura and fetal death. A 3700 gram dead male fetus without gross malformation was delivered by forceps. Post delivery abruptio placentae, diffuse intravascular coagulation, fulminant preeclampsia and acute renal failure followed.